Cerebroventricular calcitonin gene-related peptide inhibits rat duodenal bicarbonate secretion by release of norepinephrine and vasopressin.
Proximal duodenal bicarbonate secretion is an important factor in humans and animals protecting the mucosa against acid-peptic damage. This study examined the mechanisms responsible for the central nervous system regulation of duodenal bicarbonate secretion by calcitonin gene-related peptide (CGRP) in unrestrained rats. Cerebroventricular administration of rat CGRP significantly inhibited basal duodenal bicarbonate secretion as well as the stimulatory effects of vasoactive intestinal peptide, neurotensin, a luminal PGE1 analogue, misoprostol, and hydrochloric acid. The inhibitory effects of cerebroventricular CGRP were abolished by ganglionic blockade with chlorisondamine, significantly attenuated by noradrenergic blockade with bretylium, and enhanced by vagotomy. Inhibition of duodenal bicarbonate secretion induced by CGRP coincided with significant increases in plasma norepinephrine (NE) and vasopressin concentrations. The alpha adrenergic receptor antagonist, phentolamine, and the vasopressin V1 receptor antagonist, (1-deaminopenicillamine, 2-[O-methyl]Tyr, 8-Arg)-vasopressin, given intravenously reversed the central inhibitory effect of CGRP by approximately 50% each. Pretreatment of the animals with both phentolamine and the vasopressin antagonist completely abolished the central inhibitory effect of CGRP. Peripheral vasopressin and NE significantly decreased duodenal bicarbonate secretion, and their inhibitory effects were additive and prevented by phentolamine and the vasopressin antagonist, respectively. We conclude that cerebroventricular CGRP inhibits rat duodenal bicarbonate secretion by activation of sympathetic efferents and subsequent release of NE and vasopressin that act on alpha adrenergic and vasopressin receptors, respectively.
Lenz
H J
HJ
Department of Medicine, University of Hamburg, Federal Republic of Germany.
Brown
M R
MR
D000315:Adrenalectomy; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001949:Bretylium Compounds / Q000494:pharmacology*; D001950:Bretylium Tosylate / Q000494:pharmacology*; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D007016:Hypophysectomy; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014628:Vagotomy; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000502:physiology*
D001639:Bicarbonates; D001949:Bretylium Compounds; D014667:Vasopressins; D001127:Arginine Vasopressin; D009270:Naloxone; C028888:argipressin, deaminopenicillamine(1)-O-methyl-Tyr(2)-; D001950:Bretylium Tosylate; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine; D010646:Phentolamine